Disease relevance of CD3D

• SUMMARY: Two new severe combined immunodeficiency conditions have been reported as a consequence of either CD3D or CD3E deficiency [1].
• We also isolated a phage clone from the CD3D/G yeast artificial chromosome clone (yB22B2) which detects 11- and 12-kilobase mRNAs, most likely for the MLL/ALL-1 gene associated t(4;11)(q21;q23) and t(11;19)(q23;p13) translocations [2].
• Translocation of CD3D gene in an acute myeloid leukemia (M5) with t(11;17)(q23;21) [3].
• CD3 delta and TCR beta mRNA in ATL and T4 chronic lymphocytic leukemia cells were equally stable to actinomycin D treatment [4].
• In contrast, gp78 lacking an intact RING finger or its multiple membrane-spanning domains stabilizes CD3-delta. gp78 has thus been found to be an example of a mammalian cellular E3 intrinsic to the ER, suggesting a potential link between ubiquitylation, ERAD, and metastasis [5].

High impact information on CD3D

• Additionally, a deficiency of CD3 delta, a component of the T-cell antigen receptor, results in a near absence of circulating mature CD3+ T cells and a complete lack of gamma/delta T cells [6].
• Alternatively, it is possible that the cytoplasmic CD3 delta, epsilon+ fetal NK cells represent a distinct subpopulation of NK cells that is predominant in the fetus, but replaced by the cytoplasmic CD3 delta,epsilon- adult NK cell population after embryogenesis [7].
• Expression of CD3 epsilon and CD3 delta transcripts and cytoplasmic proteins in fetal NK clones was confirmed by polymerase chain reaction and Western blot analysis [7].
• Northern blot analysis of transcripts coding for CD3/TCR molecules revealed the presence of CD3 zeta, epsilon, and gamma transcripts, while CD3 delta was undetectable [8].
• In vitro expansion of CD3/TCR- human thymocyte populations that selectively lack CD3 delta gene expression: a phenotypic and functional analysis [8].

Biological context of CD3D

• We recently showed that breakpoints in four 11q23 translocations, t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13.3), were contained within a yeast artificial chromosome clone bearing the CD3D and CD3G gene loci [9].
• We have successfully applied semi-automated, fluorescence-based technology to undertake association analysis on the CD3D microsatellite [10].
• We have also performed a large case-control analysis of a restriction fragment length polymorphism (RFLP) in the CD3 epsilon (CD3E) gene, 26 kb from CD3D [10].
• We mapped the familial form by linkage analysis in 6 families to chromosome region 11q22-q23, between the markers STMY and CD3D which currently span a 16-cM interval [11].
• RECENT FINDINGS: Homozygous mutations in CD3D and CD3E genes lead to a complete block in T-cell development and thus to an early-onset severe combined immunodeficiency phenotype [1].

Anatomical context of CD3D

• Patients and affected fetuses from 2 families were homozygous for a mutation in the CD3D gene, and patients from the third family were homozygous for a mutation in the CD3E gene [12].
• CD3D probe detected the rearranged bands in DNA from two of them after digestion with NotI and SacII enzymes, demonstrating that the breakpoints of both cell lines were estimated to be within 360 kilobases of CD3D [13].
• Six T cell receptor (TCR) markers for the CD3D, TCRDVAJ, TEA, TCRBV6S1, BV6S3, BV6S7 and BV13S2 genes were analysed [14].
• These studies define Glc trimming and calnexin association as initial molecular events in the translation of CD3 delta and TCR alpha proteins occurring coincident with or immediately after their translocation into the endoplasmic reticulum and preceding the ordered pairing of TCR chains [15].
• This association was not observed on T1 hybridomas expressing only CD8 alpha alpha or a CD3 delta(-) variant of the T1 TCR [16].

Associations of CD3D with chemical compounds

• Interestingly, we found that removal of Glc residues from glycan chains was necessary for efficient association of calnexin with TCR alpha glycoproteins but not with CD3 delta glycoproteins [15].
• Site-specific mutations of the TCR-alpha charged residues within this motif (arginine, lysine) to leucine and similar point mutations of the transmembrane CD3-epsilon and CD3-delta charge groups resulted in the abrogation of assembly [17].
• In contrast, treatment of T cells with tunicamycin suggested that N-linked glycosylation of CD3 delta is required for TCR assembly [18].
• In this study the effects of A23187 and thapsigargin on the degradation of T-cell antigen receptor-beta (TCR-beta) and CD3-delta in the endoplasmic reticulum have been studied [19].
• The sigma1 proteins of T3D and T3C31 contain a threonine at amino acid position 249, whereas an isoleucine occurs at this position in the sigma1 proteins of the remaining strains [20].

Other interactions of CD3D

• The CD3D, G, and E genes have been positioned proximal to the 11q23 breakpoint of the 4;11 translocation while the THY1 and ETS1 genes have been mapped distal to this breakpoint [21].
• THY1 and CD3D genes were polymorphic after MspI digestion but no significant association was observed [22].
• Despite the presence of T-cells (CD3 delta marker) in the orbital connective tissue/fat of all five patients studied as well as in orbital muscle from one of these patients, IFN gamma reverse transcribed mRNA was notably absent from these tissues [23].
• The interaction of CD4 and CD8 with the TCR/CD3 complex during antigen recognition may thus be asymmetrical, taking place through CD3 delta and gamma, respectively [24].
• CXCL13 and CD3D were expressed in >/=90% of primary SS patients and in </=10% of the controls [25].

Analytical, diagnostic and therapeutic context of CD3D

• We show in this study, by immunoprecipitation and two-dimensional gel electrophoresis, that in the human T cell line Jurkat as well as in total human thymocytes, this preferential interaction does not occur and instead, the CD3 epsilon/CD3 gamma and CD3 epsilon/CD3 delta dimers associate with both TCR chains simultaneously and indistinctly [26].
• In situ hybridization results showed that unlike in other studied cases with rearrangements of 11q23, the CD3D gene in the t(11;17)(q23;21) is transposed to the der(17) chromosome, providing evidence for a different breakpoint in the 11q23 region [3].
• Using a nested reverse transcriptase polymerase chain reaction technique, we measured the relative mRNA levels of 10 cytokines and CD3 delta chain [27].
• These levels correlated positively with the CD3 delta-chain mRNA levels (r = 0.83) and with the T cell infiltration (r = 0.71) as determined by immunohistochemistry [28].
• The structures of reovirus serotypes T2J (Jones), T3D (Dearing) and the T3D core particle have been determined by cryo-electron microscopy and image processing [29].

References